Increasing Diversity in Clinical Studies

So what’s behind these trends? A number of factors may contribute to the health disparities based on sex, and racial or ethnic groups. For example:

• Few research studies are designed to look specifically at heart and blood vessel diseases in women, older adults (75+), and people from underrepresented racial and ethnic groups. But we now know these diseases and their treatments play out differently among these groups.
• Clinical studies have enrolled mostly White men. Historically, participation has been low among:
• Women
• Adults ages 75 and older
• People of certain racial and ethnic groups

A typical cardiovascular clinical trial often included many more men than women. In fact, women made up half of the participants in very few studies.

Even when research studies include women, sex-related differences are often not examined.

In addition, more than half of trials for coronary heart disease over a decade failed to enroll any patients over 75 years old.

Other factors are also at play including:

• Lack of trust in research studies, and questioning whether the clinician has their best interest at heart
• Fear of unintended outcomes, not wanting to be a “guinea pig”
• Not enough leaders who are from underrepresented groups in clinical trial investigations (only 1% of all principal investigators at the National Institutes of Health are Black)
• Lack of access to preventive care or specialty care centers and fewer opportunities for being referred to clinical studies
• Physician awareness about the different risks (one study found only 17% of cardiologists correctly identified that women have a higher risk for heart disease than men)

“It would be great if everything we learn from clinical research could be applied to everyone. In reality, cardiovascular disease and many other conditions are not the same across genders and racial and ethnic groups, and neither are their responses to treatment. ”– Martha Gulati, MD, associate director, Barbra Streisand Women Heart Center in Los Angeles

Research studies pave the way for new and better therapies. In recent years, the Food and Drug Administration (FDA) has called for wider representation of people of different ages, races, ethnic groups and gender in clinical studies. The goal is to ensure medical products are safe and effective for everyone.

Historically, older patients, women and people from racial or ethnic minority groups, have been underrepresented in trials. People from sexual minority groups, including transgender and non-binary communities have also been underrepresented. As a result, it’s often not until more people start using these medications after they are approved by the FDA that differences in how they work in diverse patient groups come to light.

Some drugs appear to affect men and women differently. Also, race and ethnicity can make a difference. For instance, angiotensin-converting enzyme (ACE) inhibitors have been shown in some studies to be less effective to control high blood pressure in Black patients than in White patients.

There is also some evidence that our genes play a role as well, often interacting with our diets and where we live. For example, it seems that Black Americans may be more sensitive to the effect of salt, which increases the chance of developing high blood pressure. The same salt sensitivity has been described in patients with obesity and chronic kidney disease.

At times, the FDA has required changes to drug labels because of differences in how these medications work in men and women. For example, doses of a common sleep aid were halved in women due to its more potent effects. These differences are why it’s important to test drugs on diverse patient populations.  

“We know treatments work differently in different people, so to get a complete picture of the benefits and risks of a particular therapy, people involved in clinical trials ideally need to represent everyone who is likely to use the treatment or intervention being studied,” said Keith C. Ferdinand, MD, professor of medicine, Tulane University, New Orleans.

Researchers need a large enough sample of patients to be able to draw conclusions. We have a long way to go to add more diversity into clinical research.

In 2011, African Americans made up 12% of the U.S. population, yet only 5% of clinical trial participants, according to the FDA. Hispanic people made up 16% of the population, but only 1% of studies. Meanwhile, White people were overrepresented: They accounted for 83% of participants in clinical trials and 67% of the U.S. population.

Read FDA Paper: Dialogues on Diversifying Clinical Trials

“Ignoring the racial/ethnic diversity of the U.S. population is a missed scientific opportunity to fully understand the factors that lead to disease or health.” —PLOS article

Race, ethnicity, sex and age may play a defining role in how heart disease and stroke develop, how they are detected in some cases, and how we might respond to different treatments. There are:

• Genetic variations in heart and blood vessel disease, and how it develops across ethnic groups
• Higher rates of certain diseases across certain populations
• Females have a greater risk of having a bad reaction to medications compared with males
• Black Americans have more angioedema, a potentially life-threatening condition, with certain drugs used to treat patients with heart failure (ACE-inhibitors and dual ARB/sacubutril) 

The reason people of diverse backgrounds may respond differently from others is unknown. In addition to genetics, people respond to drugs based on their body weights, diet patterns and lifestyle factors.

Many people who have participated in a clinical trial say they would do it again. Among the reasons to take part include helping to make sure treatment options continue to advance and benefit future generations.

Learn more: Visit Mended Hearts' Clinical Trials page

If you or a loved one wants to learn more about clinical trials as an option for treatment, talk with your health care team. You might want to ask:

• Would a clinical trial be a reasonable option for me?
• Will it affect my usual care?
• How does the study treatment differ from what’s currently available?
• How much time will it take?
• What are the risks?
• Can I drop out?
• How will you keep my doctor informed about my treatment?
• Are there reimbursements for travel/child care?
• Will this research help others like me in the future?